Reprogramming PBMC Bioenergetics Via Phosphoglucomutase 1 Modulation in Type 2 Diabetes: Unveiling a Glycogen-Immune Axis.

The interplay between cellular energy metabolism and immune function has gained increasing attention in type 2 diabetes mellitus (T2DM). Phosphoglucomutase 1 (PGM1), a pivotal enzyme bridging glycogen flux and glycolysis, may critically influence immune cell survival in metabolically stressed environments. To dissect the impact of PGM1 dysfunction on peripheral blood mononuclear cell (PBMC) resilience in T2DM, illuminating its role as a potential immunometabolic vulnerability. 40 T2DM patients and 40 healthy matched controls were enrolled. PGM1 enzymatic activity and mRNA expression in PBMCs were measured, alongside PBMC viability under glucose-restricted conditions to mimic metabolic stress. T2DM patients displayed markedly attenuated PGM1 activity and gene expression compared with controls, correlating with impaired PBMC survival under glucose limitation. These findings suggest a novel metabolic checkpoint governing immune competence in T2DM. PGM1 deficiency within circulating immune cells may compromise their bioenergetic adaptability, potentially increasing susceptibility to infection and systemic inflammation in diabetes. These results warrant further exploration of PGM1-directed interventions to restore immunometabolic balance in T2DM.